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Trends Mol Med. 2017 Oct;23(10):917-931. doi: 10.1016/j.molmed.2017.08.002. Epub 2017 Sep 5.

Genome Engineering for Personalized Arthritis Therapeutics.

Author information

1
Department of Orthopedic Surgery, Washington University, St. Louis, MO 63110, USA; Shriners Hospitals for Children - St. Louis, St. Louis, MO 63110, USA; Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA.
2
Department of Biomedical Engineering, Duke University, Durham, NC 27708, USA.
3
Cytex Therapeutics, Inc., Durham, NC 27705, USA.
4
Department of Orthopedic Surgery, Washington University, St. Louis, MO 63110, USA; Shriners Hospitals for Children - St. Louis, St. Louis, MO 63110, USA.
5
Department of Biomedical Engineering, Duke University, Durham, NC 27708, USA. Electronic address: Charles.gersbach@duke.edu.
6
Department of Orthopedic Surgery, Washington University, St. Louis, MO 63110, USA; Shriners Hospitals for Children - St. Louis, St. Louis, MO 63110, USA; Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA; Department of Biomedical Engineering, Duke University, Durham, NC 27708, USA; Cytex Therapeutics, Inc., Durham, NC 27705, USA. Electronic address: guilak@wustl.edu.

Abstract

Arthritis represents a family of complex joint pathologies responsible for the majority of musculoskeletal conditions. Nearly all diseases within this family, including osteoarthritis, rheumatoid arthritis, and juvenile idiopathic arthritis, are chronic conditions with few or no disease-modifying therapeutics available. Advances in genome engineering technology, most recently with CRISPR-Cas9, have revolutionized our ability to interrogate and validate genetic and epigenetic elements associated with chronic diseases such as arthritis. These technologies, together with cell reprogramming methods, including the use of induced pluripotent stem cells, provide a platform for human disease modeling. We summarize new evidence from genome-wide association studies and genomics that substantiates a genetic basis for arthritis pathogenesis. We also review the potential contributions of genome engineering in the development of new arthritis therapeutics.

KEYWORDS:

Arthritis; GWAS; autoimmune; drug screening; genome engineering; iPSC; inflammation

PMID:
28887050
PMCID:
PMC5657581
DOI:
10.1016/j.molmed.2017.08.002
[Indexed for MEDLINE]
Free PMC Article

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